Autistic Aggression & Self Injury Helped by Common Drug

April 20, 2020

High Dose Propranolol May Reduce Severe Challenging Behaviors

The common hypertension drug propranolol has been found1 to decrease aggression, self-injury and severely disruptive behavior in children and adults with autism if given in high doses. These behaviors afflict up to 68% of those with autism, with self-injurious behavior (SIB) alone affecting 42%.2

Among the study participants, the vast majority – 85% – were rated much improved or very much improved in their challenging behaviors, with 4% slightly improved and 11% not improved or worse.

“This improvement and efficacy is outstanding and would be superior to any medication currently used if this finding is confirmed with more rigorous clinical research methodologies,” state the authors.

Although not quantified, there was little to no benefit for such common autism symptoms as hyperactivity, repetitive behaviors or mood.

The average dose in which positive effects were found was 462 mg, with a range of 120 mg to 960 mg. Only a few cases responded well to doses lower than 300 mg per day. As a comparison, the normal dose of propranolol in other populations for aggressive behavior is 80-300 mg/day.3 and for hypertension the dose can go up to 320 mg/day.4

Encouraging Safety Profile

The new research reported a reassuring safety profile along with effectiveness. Doctors have been leery of propranolol in high doses due to concerns over cardiac effects. Propranolol is a beta-blocker used to treat high blood pressure, irregular heartbeats, and tremors.

Therefore, the study investigators conducted in-depth cardiology evaluations and took frequent vital signs while patients received the drug.

A chart review and discussion with caretakers did not reveal evidence of any adverse cardiorespiratory symptoms or events except for one case in which lethargy and peripheral cyanosis occurred, though it is unclear if this was related to the drug. No side effects were seen even at the highest doses given.

The investigators report that “it appears that moderate and high-dose beta blocker therapy can be given safely without adverse cardiovascular problems provided that close clinical monitoring is maintained.”

High Burden

Severe challenging behaviors such as aggression and SIB can cause significant morbidity and decrease the quality of life for individuals with autism. They are a frequent cause of hospitalization and are often the chief complaint of parents and educators, at times outweighing the core symptoms of autism as problems. As children age into adolescence and adulthood, the cost to manage these behavioral challenges increases, while the expenditures for other services that promote skills and independence decline.

Poor Alternatives

The currently available treatments for aggression and SIB are limited.

Two antipsychotic medications, risperidone and aripiprazole, are the only FDA-approved medications for the treatment of “irritability” associated with autism. Irritability includes tantrums, aggression, and SIB. These drugs are ineffective for many and have serious long term side effects.

Applied Behavior Analysis (ABA) therapy is a first line treatment and can be effective, but it is not always available due to cost or shortage of therapists, and it is not always effective5.

Before receiving propranolol, patients in the study presented with ongoing challenging behavior, yet almost all had received high quality ABA and had tried or were on standard antipsychotics. The mean number of medications previously and/or currently being tried was 6.2.

Few large, well designed treatment studies for challenging behavior have been conducted despite the need. Individuals with autism and challenging behaviors are rarely included in research studies due to their behaviors. This study is among the few to address this unmet need.

About the Drug

Propranolol, also known as Inderal, is a beta-blocker in widespread use for over 50 years. It is FDA approved for high blood pressure, irregular heartbeats, and tremors. It is sometimes used to prevent migraine headaches and chest pain. It is also given off-label for anxiety and PTSD. 3,4

Small studies over the past 30 years have reported success with propranolol for aggression in autism and other populations, such as hospitalized psychiatric patients and those with severe intellectual disability, dementia or traumatic brain injury. Other studies have shown that propranolol has benefits for autism in the areas of verbal problem solving, word fluency, facial scanning, and conversation reciprocity.

Despite these promising reports, concerns regarding the safety of high dose propranolol have limited its clinical application and it is rarely prescribed for autism.

Propranolol’s mode of action suggests why it might be effective for autism. Propranolol can easily cross the blood–brain barrier and exert effects on the brain. Anxiety is common in autism and may underlie some challenging behaviors. Propranolol blocks the neurotransmitters adrenaline and noradrenaline which contribute to the physical symptoms of anxiety. Beta blockers can dampen down stimulation of the amygdala, known to be involved in autism and in fear responses. Hyperreactive fear response may underlie some challenging behaviors. Propranolol has been shown to alter the connectivity of various brain circuits, with some increases in connectivity and some decreases. This flexibility of response may enable the individual to have a more appropriate coping mechanism for a stressor than resorting to an autonomic-driven fight or flight and then demonstrating the symptoms of aggression or SIB.

About the Study

The study, led by Barbie Zimmerman-Bier, MD and Eric London, MD, was a retrospective case series design of 46 individuals, 8 females and 38 males, with ages ranging from 8 to 32 years. Patients had been officially diagnosed with autism and had high levels of aggression, SIB, and severely disruptive behaviors. Symptom severity and medication effectiveness were quantitated using the Clinical Global Impression (CGI) scales.

The propranolol was added to the patients’ existing medications. It was generally started at low doses (eg, 10 mg, three times per day) and titrated up until acceptable benefit was observed or side effects emerged. The titration schedule varied for each patient.

Clinical Trial Underway

Following the positive results of this case-series study, the investigators have initiated a Phase 2 randomized clinical trial (RCT)6 comparing high dose propranolol to a placebo. The RCT is actively enrolling 24 participants ages 12-30 with autism residing in NJ. It should be completed in 2021.

According to the clinical trials registration page for the study, “well-designed clinical trials demonstrating the efficacy and safety of high dose propranolol will have significant effects on clinical practice and improve the physical and behavioral quality of life for an underserved subset of individuals with ASD.”


[1] Eric B. London, J. Helen Yoo, Eric D. Fethke, Barbie Zimmerman-Bier. The Safety and Effectiveness of High-Dose Propranolol as a Treatment for Challenging Behaviors in Individuals With Autism Spectrum Disorders. J Clin Psychopharmacol 2020;40: 122–129.

[2] Steenfeldt-Kristensen C, Jones CA, Richards C. The Prevalence of Self-injurious Behaviour in Autism: A Meta-analytic Study [published online ahead of print, 2020 Apr 15]. J Autism Dev Disord. 2020;10.1007/s10803-020-04443-1. doi:10.1007/s10803-020-04443-1.



[5] Strydom, A., Bosco, A., Vickerstaff, V. et al. Clinical and cost effectiveness of staff training in the delivery of Positive Behaviour Support (PBS) for adults with intellectual disabilities, autism spectrum disorder and challenging behaviour – randomised trial. BMC Psychiatry 20, 161 (2020).

[6] Propranolol for Challenging Behaviors in Autism. Identifier: NCT04047355.

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